Process for producing bipyribyls



United States Patent This invention relates to an oxidation process for the manufacture of organic bases, more particularly 4:4-

bipyridyl.

4:4-bipyridyl is a valuable intermediate for the manufacture of herbicidal products and is commonly made, in conjunction with varying proportions of isomeric materials, by oxidation of the product obtained by interaction of sodium and pyridine. An alternative method, described in copending US. application, Serial No. 193,627, filed May 9, 1962, is that of oxidising the interaction product of magnesium and pyridine. In both these methods, it has been the usual practice hitherto to oxidise the metal-pyridine interaction product with air or oxygen, since this affords a cheap method and also has been regarded as a suitable way of controlling the vigorous oxidation reaction.

Oxidation by a gaseous oxidising agent has several disadvantages, however, including in particular the explosion and fire hazard which can arise from the formation of hot mixtures containing oxygen and organic vapours (for example from the hydrocarbon diluents employed) in the reaction vessels. This hazard is increased by the possible presence of finely divided metal. Furthermore, the large volume of nitrogen associated with the oxygen, or added .to reduce fire hazard, reduces the efliciency of the condensers used in the process.

According to the present invention there is provided an improved process for the manufacture of bipyridyls wherein a metal-pyridine interaction product is treated with nitric acid.

The reaction which takes place is vigorous but, surprisingly, is very readily controlled and does not lead to additional formation of undesired by-products from the pyridine. The yield of bipyridyls is good, and the disadvantages of the earlier oxidation methods are avoided without loss of yield of product. Also, the products to which the nitric acid is converted during the reaction are substantially all gaseous or water-soluble and these, together with the metal nitrates also formed, are very readily eliminated in subsequent isolation procedures.

The metal-pyridine interaction product may be in particular a sodium-pyridine interaction product, which may be prepared in known manner by mixing finely divided sodium With the pyridine in an inert diluent for example xylene or petroleum spirit. Other alkali metals, for example potassium and lithium, may also be used in place of sodium, though these are less convenient and accessible. There may be used a magnesium-pyridine interaction product, which may be prepared in the manner described in co-pending U.K. application No. 18,166/ 61 by interacting magnesium metal with the pyridine, preferably in the presence of a small proportion of an initiator which may be in particular a material which can induce the formation of free radicals in the magnesium-pyridine mixture, for example iodine, bromine, or finely divided sodium or potassium. There may also be used an aluminium-pyridine interaction product, which may be prepared by interacting aluminium metal with the pyridine, preferably in the presence of an initiator, for example a material which can initiate a magnesium-pyridine interaction and/or a material which can clean the metal by 3,210,353 Patented Oct. 5, 1965 breaking down the surface oxide film (particularly a mercury compound, for example mercuric chloride).

The pyridine used in the formation of the metalpyridine interaction product should be as free as possible from any substituent or impurity (for example, piperidine) which can take part in any undesirable sidereaction with the metal (or the initiator, when one is used). The process of our invention is especially applicable to interaction products derived from pyridine itself. Pyridines containing hydrocarbon radicals (particularly alkyl radicals, for example methyl and/or ethyl radicals) may also be used, for example picolines and lutidines; as these are less reactive than pyridine itself, however, they are better used as alkali metal interaction products.

Commonly a mixture of isomeric bipyridyls is produced by the process of the present invention, the principal constituents being the 2:2-, 2:4'- and 4:4'-isomers or such of these as are permitted by the. structure of the pyridine used as starting material in making the metal-pyridine interaction product. The 4:4'-isomer usually predominates.

The nitric acid may be used as the substantially anhydrous acid or as a solution in a diluent, especially water. When water is present, the proportion of nitric acid should in general be at least 0.2' mole, andpreferably between 0.2 and 0.5 mole, for each equivalent of metal used in making the metal-pyridine interaction product. Larger proportions may be used if desired, especially when substantially no Water is present, though this may result in a greater consumption of alkali for any subsequent isolation procedure involving neutralisation or liberation of the bases from their salts and under vigorous oxidation conditions some of the pyridine and dipyridyl may be destroyed. Nitric acid containing dissolved oxides of nitrogen is suitable for use in this process. It is generally preferred to use substantially anhydrous acid in order .to minimise the interference of water in the isolation of the product and recovery ofunused pyridine.

The nitric acid reacts immediately and the vigorous reaction can readily be controlled by adding the nitric acid at such a rate that the reaction is maintained. Most conveniently, the reaction can be carried out in a reflux apparatus, the nitric acid being added gradually to the stirred reaction mixture at such a rate that the mixture boils steadily and the condensing system is not overloaded.

Since much heat is evolved on neutralising nitric acid with a pyridine, as occurs when nitric acid is introduced into a mixture of the metal-pyridine interaction product containing excess of the pyridine, it is possible to reduce the evolution of heat during the process of the present invention by adding the nitric acid in a previously neutralised form. For this modification of the process of the present invention, the nitric acid may be partially or completely neutralised with an organic base, preferablya weak organic base, such as a pyridine or an NzN-dialkyl arylamine for example NzN-dimethyl-aniline. As the nitrate of the base maybe solid and tend to interfere with the ease of addition of the reactant, the mixture of nitric acid and base may be diluted, for example with water, to produce a homogeneous and/or fluid phase more suitable for addition to the metal-pyridine interaction product. If this method of addition is to be, adapted, it is preferred to use an organic base which does not interfere with the isolation of the bipyridyls or the recovery of unchanged pyridine for re-use. The most suitable base is the pyridine itself, as this does not complicate the isolation and recovery procedures by the presence of additional basic components.

The isolation of bipyridyls from the reaction mixture can be carried out by conventional techniques, for example fractional distillation, extraction with acid and treatment of the acid extracts with alkali, fractional crystallisation, and combinations of such techniques. The mixture of isomeric bipyridyls may be used as such, or may be separated by the known methods in order to obtain individual isomers, particularly 4:4'-bipyridyl, in a substantially pure state.

The process of the present invention has the advantage of rapid, smooth and complete reaction while retaining ease of control. This is especially important in commercial operation, as production from a given installation can be increased and the process is suitable for continuous operation. Moreover, the explosion and fire hazard are very greatly reduced because the large volumes of gaseous oxidising medium previously required now are avoided and the reaction can be carried out in an inert atmosphere, for example under nitrogen. The losses of material and the cost of refrigeration, resulting from the large flow of gases in the prior art processes, are also largely eliminated, and the cost and complexity of the isolation procedure is greatly reduced by the fact that most of the inorganic by-products are in gaseous or water-soluble form.

The bypyridyls are useful as intermediates in chemical synthesis and in the manufacture of herbicidal products.

The invention is illustrated but not limited by the following examples in which the parts and percentages are by weight.

Example 1 12.2 grams (0.5 mol) of magnesium turnings, 100 grams of N:N-dimethylaniline and 79 grams (1.0 mol) of pyridine were mixed and reaction was started by the addition of 1 gram of a dispersion of sodium in trimethylbenzene, containing 33% of sodium metal. The mixture was then stirred and boiled under reflux conditions in an atmosphere of nitrogen for 5 hours. The reaction mixture was then oxidised by gradual addition, with stirring, of 6.3 grams (0.07 mol) 'of 70% nitric acid during minutes while the temperature of the mixture was maintained at 100 C.110 C. The product was cooled and was found by analysis to contain 7.2 grams of unreacted magnesium, 64 grams of pyridine, 0.4 gram of 2:4'-bipyridyl and 16.4 grams of 4 4'-bipyridyl.

Example 2 7 grams of magnesium turnings and 176.5 grams of pyridine were mixed and reaction was started by the addition of 0.9 gram of a dispersion of sodium in trimethylbenzene, containing 33% of sodium metal. The mixture was then stirred and boiled under reflux for 5 hours, after which time the reaction mixture was cooled to 60 C. and maintained at this temperature by appropriate cooling while 23 grams of 41% aqueous nitric acid were added gradually with stirring. An atmosphere of nitrogen was maintained in the reaction vessel throughout these operations. The resulting product (252 grams) contained 60.1% pyridine, 0.3% 2:4'-bipyridyl, and 6.9% 4:4'-bipyridyl, The yield of bipyridyls was 25% of theory based on the pyridine consumed and 73% of theory based on the magnesium consumed.

Example 3 The procedure of Example 2 was repeated except that the reaction mixture was maintained at a temperature of 80 C. while the nitric acid addition was made. The yield of 4:4-bipyridyl was 26% of theory based on the pyridine consumed and 55% of theory based on the magnesium consumed.

Example 4 The procedure of Example 2 was repeated except that the reaction mixture was maintained at boiling point under reflux conditions while the oxidation by the addition of the nitric acid was carried out.

' 20 minutes.

Example 5 Pyridine (100 parts) was mixed cautiously with nitric acid (20 parts), with cooling by ice water. Pyridine nitrate crystallised as a white solid from the resulting mixture, and was collected by filtration. Residual pyridine was removed from the solid by washing with acetone, and the product was then dried in vacuo.

Sodium metal (11.5 parts, 0.5 atomic proportion) in the form of a 33% dispersion in trimethylbenzene, was added in portions, with stirring, to pyridine (316 parts, 4 moles) during 30 minutes while the temperature of the mixture was maintained at to C. by appropriate cooling. The mixture was maintained at 90 C. for a further 30 minutes after addition of the sodium was complete, and was then oxidised by the addition of pyridine nitrate (55 parts, 0.25 mole) which had been prepared as described above, in portions of l to 2 parts at a time over a period of The resulting product (weighing 378 parts) contained 54% pyridine, 8.3% of 4:4'-bipyridyl, and 1.9% of 2:4'-bipyridyl. The yield of 4:4'bipyridyl corresponded to 30% of theory based on the pyridine consumed.

What we claim is:

1. In a process for preparing a bipyridyl selected from the group consisting of unsubstituted bipyridyls and alkylsubstituted bipyridyls by reacting a metal with a compound selected from the group consisting of pyridine and alkyl derivatives thereof, followed by oxidation of the resulting metal-pyridine interaction product to yield the bipyridyl, the improvement which comprises oxidizing the metal-pyridine interaction product by the addition of nitric acid to the reaction mixture containing the interaction product to form the bipyridyl, and thereafter recovering the bipyridyl by isolation from the reaction mixture.

2. Process as claimed in claim 1 wherein the proportion of nitric acid is at least 0.2 mole for each equivalent of metal used in making the metal-pyridine interaction product.

3. Process as claimed in claim 2 wherein the proportion of nitric acid is between 0.2 and 0.5 mole for each equivalent of metal used in making the metal-pyridine interaction product.

4. Process as claimed in claim 1 wherein the nitric acid is added to the metal-pyridine interaction product in a previously neutralised form.

5. Process as claimed in claim 4 wherein the nitric acid is at least partially neutralized with an organic base selected from the group consisting of a pyridine and an NzN-dialkyl arylamine.

6. Process as claimed in claim 5 wherein the organic base is the pyridine from which the metal-pyridine interaction product is derived.

7. Process as claimed in claim 1 wherein the metalpyridine interaction product is a sodium-pyridine interaction product.

8. Process as claimed in claim 1 wherein the metalpyridine interaction product is a magnesium-pyridine interaction product.

9. Process as claimed in claim 1 wherein the metalpyridine interaction product is an aluminium-pyridine interaction product.

10. Process as claimed in claim 1 wherein the metalpyridine interaction product is derived from pyridine itself.

11. A process for preparing 4:4'-bipyridyl which comprises reacting pyridine and magnesium in the presence of excess pyridine and an alkali metal iniitator, at reflux c011 ditions in an inert atmosphere to form a reaction mixture containing a magnesium-pyridine interaction product, and. then oxidizing the resulting interaction product by the C. and the boiling point thereof to form an oxidation product consisting primarily of said 4:4-bipyridy1, and thereafter recovering the oxidation product by isolation from the reaction mixture.

12. A process for preparing 4:4-bipyridy1 which comprises reacting pyridine and an alkali metal in the presence of excess pyridine while maintaining the temperature of the reaction within the range of about 90 to 100 C. to form a reaction mixture containing an alkali metalpyridine interaction product, and then oxidizing the interaction product by the gradual addition of at least 0.2 mol of pyridine nitrate for each equivalent of alkali metal reacted while maintaining the temperature within the range of 90 and 100 C. to form an oxidation product consisting primarily of said 4:4'-bipyridyl, and thereafter recovering the oxidation product by isolation from the reaction mixture.

References Cited by the Examiner WALTER A. MODANCE, Primary Examiner. 

1. IN A PROCESS FOR PREPARING A BIPYRIDYL SELECTED FROM THE GROUP CONSISTING OF UNSUBSTITUTED BIPYRIDYLS AND ALKYLSUBSTITUTED BIPYRIDYLS BY REACTING A METAL WITH A COMPOUND SELECTED FROM THE GROUP CONSISTING OF PYRIDINE AND ALKYL DERIVATIVES THEREOF, FOLLOWED BY OXIDATION OF THE RESULTING METAL-PYYRIDINE INTERACTION PRODUCT TO YIELD THE BIPYRIDYL, THE IMPROVEMENT WHICH COMPRISES OXIDIZING THE METAL-PYRIDINE INTERACTION PRODUCT BY THE ADDITION OF NITRIC ACID TO THE REACTION MIXTURE CONTAINING THE INTERACTION PRODUCT TO FORM THE BIPYRIDYL, AND THEREAFTER RECOVERING THE BIPYRIDYL BY ISOLATION FROM THE REACTION MIXTURE. 